Pain
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Animal studies have suggested that the cerebellum, in addition to its motor functions, also has a role in pain processing and modulation, possibly because of its extensive connections with the prefrontal cortex and with brainstem regions involved in descending pain control. Consistently, human imaging studies have shown cerebellar activation in response to painful stimulation. However, it is presently not clear whether cerebellar lesions affect pain perception in humans. ⋯ In contrast, heat and pressure pain thresholds were not significantly different between groups. These results show that, after cerebellar infarction, patients perceive heat and repeated mechanical stimuli as more painful than do healthy control subjects and have deficient activation of endogenous pain inhibitory mechanisms (offset and placebo analgesia). This suggests that the cerebellum has a previously underestimated role in human pain perception and modulation.
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Randomized Controlled Trial
Fasinumab (REGN475), an Antibody against Nerve Growth Factor for the Treatment of Pain: Results from a Double-Blind, Placebo-Controlled Exploratory Study in Osteoarthritis of the Knee.
The safety, tolerability, and efficacy of fasinumab (REGN475), a fully human monoclonal antibody against nerve growth factor, was evaluated for the treatment of pain in patients with osteoarthritis (OA) of the knee. This was a 24-week, double-blind, placebo-controlled, parallel-group, repeat-dose, exploratory study. Eligible patients 40 to 75 years of age with a diagnosis of OA of the knee and moderate to severe pain were randomized 1:1:1:1 to intravenous fasinumab 0.03, 0.1, or 0.3 mg/kg or placebo and received study drug on day 1 and day 57. ⋯ Discontinuation for TEAEs occurred in 5.6% of fasinumab patients and 3.7% of placebo patients. All 3 doses of fasinumab were associated with significant (P<.05) improvements compared with placebo in walking knee pain and WOMAC total and subscale scores. Fasinumab was generally well tolerated, and was associated with a significant reduction in walking knee pain and an improvement in function for up to 8 weeks.
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Patient ratings of satisfaction with their postoperative pain treatment tend to be high even in those with substantial pain. Determinants are poorly understood and have not previously been studied in large-scale, international datasets. PAIN OUT, a European Union-funded acute pain registry and research project, collects patient-reported outcome data on postoperative day 1 using the self-reported International Pain Outcome Questionnaire (IPO), and patient, clinical, and treatment characteristics. ⋯ Effects were highly consistent across centres and countries. We conclude that satisfaction with postoperative pain treatment is associated with the patients' actual pain experience, but more strongly with impressions of improvement and appropriateness of care. To the degree they desire, patients should be provided with information and involved in pain treatment decisions.
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Vulvodynia is a prevalent vulvovaginal pain condition that interferes with women's psychological health. Given the central role of sexuality and relationships in vulvodynia, relationship satisfaction may be an important moderator of daily partner responses to this pain and associated negative sequelae, such as depression. ⋯ Relationship satisfaction on the preceding day moderated the associations between partner responses and women's depressive symptoms in several significant ways: (1) On days after women reported higher relationship satisfaction than usual, their perception of greater facilitative male partner responses was associated with their decreased depression; (2) on days after women reported lower relationship satisfaction than usual, their perception of greater negative male partner responses was associated with their increased depression; (3) on days after men reported higher relationship satisfaction than usual, their self-reported higher negative responses were associated with decreased women's depression, and higher solicitous responses were associated with increased women's depression, whereas (4) on days after men reported lower relationship satisfaction than usual, their self-reported higher negative responses were related to increased women's depression, and higher solicitous responses were associated with decreased women's depression. Targeting partner responses and relationship satisfaction may enhance the quality of interventions aimed at reducing depression in women with vulvodynia.
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Headaches are thought to result from the activation and sensitization of nociceptors that innervate deep cephalic tissues. A large body of evidence supports the view that some types of headaches originate intracranially, from activation of sensory neurons that innervate the cranial meninges. However, the notion of an extracranial origin of headaches continues to be entertained, although the identity of deep extracranial cephalic tissues that might contribute to headaches remains elusive. ⋯ In behavioral studies, inflammatory stimulation of these afferents promoted periorbital tactile hypersensitivity, a sensory change linked to primary headaches. Activation and sensitization of calvarial periosteal afferents could play a role in mediating primary headaches of extracranial and perhaps also intracranial origin, as well as secondary headaches such as postcraniotomy and posttraumatic headaches. Targeting calvarial periosteal afferents may be effective in ameliorating these headaches.